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The enzyme that copies methylation marks onto newly made DNA, keeping genes silenced. Azacitidine and decitabine trap and destroy it, waking silenced tumour suppressor genes in blood cancers.
DNMT1 maintains DNA methylation by copying the pattern from the parent strand to the new strand after replication. Azacitidine and decitabine are cytidine analogues incorporated into DNA that covalently trap DNMT1, which is then degraded, so methylation is lost over successive cell divisions and silenced genes are re-expressed; at higher doses they are also directly cytotoxic. They are standard treatment for higher-risk myelodysplastic syndromes and, with venetoclax, for older or unfit patients with acute myeloid leukaemia. Oral decitabine with cedazuridine matches intravenous exposure.
In plain words · The enzyme that copies methylation marks onto newly made DNA, keeping genes silenced. Azacitidine and decitabine trap and destroy it, waking silenced tumour suppressor genes in blood cancers.
The enzyme that copies methylation marks onto newly made DNA, keeping genes silenced. Azacitidine and decitabine trap and destroy it, waking silenced tumour suppressor genes in blood cancers.
Maintenance DNA methyltransferase acting at hemimethylated CpG sites after replication; covalently trapped by incorporated azacytosine.
No product in this corpus aims at DNMT1 (DNA methyltransferase 1) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Broadly expressed or essential: HPA lists DNMT1 among essential proteins and finds the RNA at low tissue specificity; the 2 medicines aimed at it (Azacitidine, Decitabine) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA DNMT1: RNA low tissue specificity; high antibody staining in 5 normal tissues; highest cancer staining lymphoma (1 of 12 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Myeloid neoplasms, Leukaemia); Open Targets associates it with 4 specific cancer types at or above 0.5 (acute myeloid leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, myelodysplastic syndrome with excess blasts). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas DNMT1 tissue; Open Targets ENSG00000130816 associations
First described 1992. Earliest sequence paper UniProt cites for the protein: Yen R.-W.C. et al, Nucleic Acids Res, 1992, "Isolation and characterization of the cDNA encoding human DNA methyltransferase". Source.
Maintenance DNA methyltransferase acting at hemimethylated CpG sites after replication; covalently trapped by incorporated azacytosine.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Appendix, Skin.
Medium only: breast cancer, cervical cancer, colorectal cancer, endometrial cancer.
HPA DNMT1 tissue · HPA DNMT1 pathology · HPA protein class: Essential proteins, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Metastatic cancer | all% | Housekeeping enzyme present in every dividing cell (methylation maintenance during replication); not a selection marker, which is why these drugs are given by cancer type rather than by test. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"DNMT1" OR ABSTRACT:"DNMT1" OR TITLE:"DNA methyltransferase 1" OR ABSTRACT:"DNA methyltransferase 1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about DNMT1 (DNA methyltransferase 1), not a curated reading list.
Shares Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Azacitidine, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.
Shares Azacitidine, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.
Shares Decitabine, Azacitidine, Myelodysplastic syndromes / neoplasms (MDS).
Shares Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Azacitidine, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.
Shares Decitabine, Azacitidine, Acute myeloid leukaemia.
Shares Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Azacitidine, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.
Shares Decitabine, Acute myeloid leukaemia.
Shares Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.